Blood ordering from the operating room: turnaround time as a quality indicator.

BACKGROUND: Quality indicators in transfusion medicine are necessary for patient safety and customer satisfaction. The turnaround time (TAT) of issuing red blood cells (RBCs) has emerged as a quality indicator but is not an established benchmark. We examined the TAT for issuing RBCs from the blood bank to the operating rooms (ORs) at Vanderbilt University Medical Center (VUMC) and Stanford University Medical Center (SUMC). STUDY DESIGN AND METHODS: TAT was defined from time of request to when RBCs exited the blood bank. Cases eligible for analysis had completed type-and-screen results with requests for four or fewer RBC units. Patients with a positive antibody screen had serologically crossmatched units prepared and reserved for intraoperative use. We also e-mailed surveys to academic institutions to establish the current state of TAT monitoring and to anesthesiologists at VUMC to gauge the TAT expectations of the OR. RESULTS: The mean TATs at the two institutions were comparable (VUMC, 10 ± 3.8 min; SUMC, 14 ± 7.2 min) for orders of RBCs. The most common reasons for delayed TAT were overlapping orders, medical technologists occupied by phone calls, and oversaturation of pneumatic tube stations. Only 3 of 24 surveyed institutions actively monitored RBC TAT. Surveyed anesthesiologists (n = 7) reported an expectation for RBC TAT of 5 to 15 minutes for urgent cases. Established internal TAT policies were 15 and 20 minutes at VUMC and SUMC, respectively, for crossmatched RBC requests for patients with complete diagnostic testing. CONCLUSION: Many of the surveyed institutions do not monitor stat RBC issue TAT as a quality indicator. This study serves as a starting point for establishing a benchmark for TAT for issuing RBCs from the blood bank to ORs.

Anti-Ge3 causes late-onset hemolytic disease of the newborn: the fourth case in three Hispanic families.

BACKGROUND: The Gerbich (Ge) blood group system consists of 11 antigens carried on red blood cell (RBC) membrane glycophorins C and D; of these, Ge:3 antigen is of high prevalence, and the anti-Ge3 is found to be clinically significant. CASE REPORT: A 34-week neonate born to a Hispanic mother with anti-Ge3 developed late-onset hemolysis with hyperbilirubinemia and was successfully treated with transfusions from her mother. Relevant clinical findings and laboratory results for this case are summarized and compared to three other previously reported cases; all babies were born from a mother of Hispanic ethnicity. CONCLUSION: Hemolytic disease of the fetus and new born associated with anti-Ge3 is rare but should be considered when working up a broadly reactive RBC antibody screen in women of Hispanic ethnicity. Early identification of pregnant women with anti-Ge3 is recommended for prenatal transfusion planning and close monitoring of the newborn infant for evidence of late-onset anemia.

Complement (C1q) fixing solid-phase screening for HLA antibodies increases the availability of compatible platelet components for refractory patients.

BACKGROUND: Immune refractoriness to platelet (PLT) transfusion is primarily due to HLA antibody. Patients at our institution are identified as refractory due to HLA by a Luminex-based immunoglobulin (Ig)G-single-antigen-bead (SAB) assay, but in highly sensitized patients, antigen-negative compatible donors cannot be found due to the high sensitivity of the IgG-SAB method. We developed an assay that detects only HLA antibodies binding the first complement component (C1q). We hypothesized that the C1q-SAB method might be more relevant than the IgG-SAB method because the antibodies identified may activate the complement cascade causing PLT destruction. STUDY DESIGN AND METHODS: Thirteen highly sensitized refractory patients received 177 PLT units incompatible by the IgG-SAB method. They were retrospectively retested by the C1q-SAB method. Calculated percent reactive antibody (CPRA) and HLA antibody specificities were compared between the two methods and corrected count increment (CCI) values were analyzed. Additionally the impact of ABO compatibility on CCI responses was evaluated. RESULTS: The mean CPRA value was significantly lower by C1q-SAB (60%) than by IgG-SAB (94%; p < 0.05). Patients showed significantly better CCI (10.6 × 10(9) ± 0.8 × 10(9) /L) with C1q-compatible (n = 134) than with C1q-incompatible PLTs (n = 43) (2.5 × 10(9) ± 0.9 × 10(9) /L/m(2) ; p < 0.0001). ABO compatibility did not significantly impact the CCI values (p < 0.0001). Our results show that 75% of PLT units previously considered incompatible were actually compatible. CONCLUSION: For highly refractory patients to PLT transfusion, the C1q-based SAB binding assay may be a better method for identifying clinically relevant HLA antibodies and selecting PLT units that will result in acceptable CCI.

How we treat: transfusion medicine support of obstetric services.

BACKGROUND: Obstetric services depend on the transfusion service (TS) to provide diagnostic testing and blood component therapy for clinical care pathways. STUDY DESIGN AND METHODS: We describe three quality improvement (QI) initiatives implemented to improve TS support of obstetric services. RESULTS: We implemented a pathway for patients requiring an ABO/Rh order for every admission to obstetric services, along with reconciliation of the daily hospital birth manifest and TS umbilical cord log to identify every woman eligible for RhIG. After assessment over 6 months, 21 (1%) of 2041 women lacked an admission ABO/Rh; all subsequently had ABO/Rh determinations. Umbilical cords were missing for eight (0.4%) mothers; four were D- and received RhIG. We developed algorithms for diagnostic blood ordering for patients deemed at "low,""moderate," or "high" risk of blood transfusion. A 27% reduction in total diagnostic test volumes and 24% reduction in charges was documented after compared to before implementation. We analyzed the impact of our massive transfusion protocol (MTP) on blood inventory management for 31 (0.25%) women undergoing 12,945 deliveries, representing 11% of 286 MTPs for all clinical services over a 32-month interval. O- uncrossmatched red blood cells (RBCs) represented 103 (24%) of 421 RBC units issued. Wastage rates of RBCs, plasma, and platelets ordered and issued in the MTPs were 0.7, 16, and 3%, respectively. CONCLUSION: QI initiatives for RhIG prophylaxis, diagnostic blood test ordering, and MTP improve TS support of obstetric services.

Quality management in the transfusion service: case studies in process improvement.

BACKGROUND: Laboratory-based quality improvement (QI) initiatives can improve clinical outcomes and patient safety. STUDY DESIGN AND METHODS: We present three cases of QI that impact processes from the transfusion service (TS) laboratory to the patient's bedside. RESULTS: Case 1 was event discovery reporting (EDR). We were able to reduce our biologic product deviation reports from 41 (17%) of 238 EDRs to only 19 (7%) of 272 (p < 0.01) EDRs after implementation of a QI workflow process. Case 2 was antibody evaluation before elective surgery. We implemented process improvement strategies: 1) surgical safety checklist with confirmation of type-and-screen completion and antibody evaluation before patients can proceed to surgery; 2) specimen retention policy of 30 days to allow advance testing; and 3) daily review to identify specimens needed on day of surgery. After intervention, only 7 (0.3%) of 2298 patients required antibody evaluation on day of surgery, compared to 65 (0.75%) of 8656 patients (p < 0.01) before intervention. Case 3 was wrong blood in tube (WBIT). We have a two-specimen requirement for blood type verification before transfusion. To determine whether trauma patients should be exempted, we reviewed WBIT errors. Six WBIT errors were from the emergency department (an error rate of 1:400) and nine WBIT specimens were institution-wide. Three patients were transfused after correction of the WBIT error. Based on this analysis, our institution agreed that no clinical units shall be exempted from our policy. CONCLUSION: Successful QI in the TS improves processes that promote efficiency, effectiveness, and patient safety.

High oxygen partial pressure decreases anemia-induced heart rate increase equivalent to transfusion.

BACKGROUND: Anemia is associated with morbidity and mortality and frequently leads to transfusion of erythrocytes. The authors sought to directly compare the effect of high inspired oxygen fraction versus transfusion of erythrocytes on the anemia-induced increased heart rate (HR) in humans undergoing experimental acute isovolemic anemia. METHODS: The authors combined HR data from healthy subjects undergoing experimental isovolemic anemia in seven studies performed by the group. HR changes associated with breathing 100% oxygen by nonrebreathing facemask versus transfusion of erythrocytes at their nadir hemoglobin concentration of 5 g/dl were examined. Data were analyzed using a mixed-effects model. RESULTS: HR had an inverse linear relationship to hemoglobin concentration with a mean increase of 3.9 beats per min per gram of hemoglobin (beats/min/g hemoglobin) decrease (95% CI, 3.7-4.1 beats/min/g hemoglobin), P < 0.0001. Return of autologous erythrocytes significantly decreased HR by 5.3 beats/min/g hemoglobin (95% CI, 3.8-6.8 beats/min/g hemoglobin) increase, P < 0.0001. HR at nadir hemoglobin of 5.6 g/dl (95% CI, 5.5-5.7 g/dl) when breathing air (91.4 beats/min; 95% CI, 87.6-95.2 beats/min) was reduced by breathing 100% oxygen (83.0 beats/min; 95% CI, 79.0-87.0 beats/min), P < 0.0001. The HR at hemoglobin 5.6 g/dl when breathing oxygen was equivalent to the HR at hemoglobin 8.9 g/dl when breathing air. CONCLUSIONS: High arterial oxygen partial pressure reverses the heart rate response to anemia, probably because of its usability rather than its effect on total oxygen content. The benefit of high arterial oxygen partial pressure has significant potential clinical implications for the acute treatment of anemia and results of transfusion trials.

Impact of cytomegalovirus (CMV) antibody reflex testing in the transfusion service on management of CMV-seronegative blood inventory.

BACKGROUND: Our goal is to minimize unnecessary cytomegalovirus (CMV)-seronegative blood transfusion to preserve the CMV-seronegative blood inventory for patients who are identified as CMV seronegative. STUDY DESIGN AND METHODS: We implemented a CMV antibody reflex testing protocol for patients who require CMV-compatible blood but in whom a CMV serostatus is unknown (coded as CMVT in our computer system). A solid-phase red blood cell (RBC) adherence antibody detection system was validated to detect CMV antibodies in plasma samples (received for ABO/Rh type and RBC antibody screen) with acceptable sensitivity and specificity. We evaluated the impact of this CMV antibody reflex testing on the management of RBC and platelet (PLT) inventory for patients requiring CMV-compatible blood. RESULTS: Over a 16-month period, implementation of CMV antibody reflex testing identified 361 (34%) of 1063 previously CMV-untested patients who required CMV-compatible blood and who were CMV seronegative. We observed a 75% decrease in the number of CMVT patients in our data base from 190 per month before implementation to 57 at 16 months postimplementation. Consequently we reevaluated the percentage in our blood inventory of CMV-seronegative units required while potentially saving 1234 CMV-seronegative blood products (835 RBCs and 399 PLTs) each month. CONCLUSION: A strategy of performing CMV antibody reflex testing in the transfusion service allows more effective blood inventory management and control in maintaining a CMV-seronegative blood inventory dedicated for patients who truly require it.

Implementation of a two-specimen requirement for verification of ABO/Rh for blood transfusion.

BACKGROUND: This study presents our implementation of a two-specimen requirement with no prior record of ABO/Rh to verify patients' blood type before transfusion. MATERIALS AND METHODS: Blood type verification was introduced, discussed, approved, and implemented over a 12-month period (May 2007 to May 2008). Potential barriers and impact on benchmark indicators were identified and tracked. RESULTS: Inpatient identification and/or specimen labeling for nursing and laboratory phlebotomists baseline corrected error rates were 1:467 and 1:5555, respectively. This study therefore sought and obtained approval to initiate a new policy of blood type verification before blood transfusion. Compliance in turnaround time (TAT) before and after implementation for completion of STAT type and screen/crossmatch within 60 minutes worsened marginally, from 90% to 80%. The impact on use of O-, uncrossmatched blood was found to be manageable. Seven (of 25 total) recorded electronic complaints were received after implementation. The corrected error rate for nurse phlebotomy draws after implementation was 1:630. CONCLUSION: Despite the lack of an instigating event, verification of blood type before blood transfusion was successfully implemented. An impact on resources and benchmark indicators such as TAT can be anticipated and managed. Further process improvement efforts will be needed to ensure safety (e.g., at time of blood transfusion) for patients receiving blood transfusions. ABO/Rh verification may be necessary even after future implementation of bar coding and/or RFID chips, because human errors continue to occur even with systems improvements.

How we treat: management of life-threatening primary postpartum hemorrhage with a standardized massive transfusion protocol.

Management of massive, life-threatening primary postpartum hemorrhage in the labor and delivery service is a challenge for the clinical team and hospital transfusion service. Because severe postpartum obstetrical hemorrhage is uncommon, its occurrence can result in emergent but variable and nonstandard requests for blood products. The implementation of a standardized massive transfusion protocol for the labor and delivery department at our institution after a maternal death caused by amniotic fluid embolism is described. This guideline was modeled on a existing protocol used by the trauma service mandating emergency release of 6 units of group O D- red cells (RBCs), 4 units of fresh frozen or liquid plasma, and 1 apheresis unit of platelets (PLTs). The 6:4:1 fixed ratio of uncrossmatched RBCs, plasma, and PLTs allows the transfusion service to quickly provide blood products during the acute phase of resuscitation and allows the clinical team to anticipate and prevent dilutional coagulopathy. The successful management of three cases of massive primary postpartum hemorrhage after the implementation of our new massive transfusion protocol in the maternal and fetal medicine service is described.

Cold agglutinin syndrome in pediatric liver transplant recipients.

Anemia is a common finding in post-liver transplant patients. Causes for the anemia include nutritional deficiencies, red cell aplasia as well as immune-mediated hemolysis. One of the immunologic causes of hemolytic anemia is drug-induced hemolysis. Tacrolimus is a common immunosuppressant used in post-liver transplant patients to prevent graft rejection. There have been reports of tacrolimus-associated hemolytic anemia secondary to hemolytic uremic syndrome as well as autoimmune hemolysis. There are also case-reports of severe hemolytic anemia related to cold agglutinin production in post-liver transplant patients. We described in this paper three cases of severe cold agglutinin hemolytic anemia in three pediatric liver transplant patients. Steroid therapy, plasmapheresis and withdrawal of tacrolimus led to resolution of the severe hemolytic process in each case. Whether the immune-mediated hemolysis is related to tacrolimus is not clear and needs to be characterized further.

Viability of red cells prepared with S-303 pathogen inactivation treatment.

BACKGROUND: A nucleic acid-targeted pathogen inactivation process with S-303 was developed to treat red blood cells (RBCs). STUDY DESIGN AND METHODS: Three studies in healthy subjects investigated posttransfusion recovery, life span, and immunogenic potential of autologous RBCs treated with S-303 and stored for 35 days. A two-arm trial in 42 subjects (1A) examined recovery of 35-day-old S-303 RBCs after a single transfusion. A one-arm study (1B) measured recovery and immune response in 28 subjects after multiple transfusions of S-303 RBCs. A randomized, crossover study (1C) in 29 subjects compared recovery and life span of 35-day-old S-303 RBCs and conventional RBCs. RESULTS: In Studies 1A and 1B, mean recovery of S-303 RBCs ranged from 78.7 to 84.4 percent. In Phase 1C, the mean 24-hour posttransfusion recoveries of S-303 and untreated RBCs were 81.7 +/- 6.3 and 84.5 +/- 6.2 percent (p = 0.05). The median life spans (t(1/2)) of S-303 and control RBCs were identical (37.4 days, p = 0.98). No antibodies to S-303 RBCs were detected. CONCLUSION: The mean 24-hour recovery of 35-day-old S-303 RBCs was less than untreated RBCs, but greater than 75 percent. RBCs treated with S-303 and stored for 35 days exhibited median life span not different from that of conventional RBCs.

Oxygen reverses deficits of cognitive function and memory and increased heart rate induced by acute severe isovolemic anemia.

BACKGROUND: Erythrocytes are transfused to improve oxygen delivery and prevent or treat inadequate oxygenation of tissues. Acute isovolemic anemia subtly slows human data processing and degrades memory, increases heart rate, and decreases self-assessed energy level. Erythrocyte transfusion is efficacious in reversing these effects of acute anemia. We tested the hypothesis that increasing arterial oxygen pressure (Pao2) to 350 mmHg or greater would supply sufficient oxygen to be equivalent to augmenting hemoglobin concentration by 2-3 g/dl and thus reverse the effects of acute anemia. METHODS: Thirty-one healthy volunteers, aged 28 +/- 4 yr (mean +/- SD), were tested with verbal memory and standard, computerized neuropsychologic tests before and twice after acute isovolemic reduction of their hemoglobin concentration to 5.7 +/- 0.3 g/dl. Two sets of tests were performed in randomized order at the lower hemoglobin concentration: with the volunteer breathing room air or oxygen. The subject and those administering the tests and recording the results were unaware which gas was administered. As an additional control for duration of the experiment, 10 of these volunteers also completed the same tests on a separate day, without alteration of hemoglobin concentration, at times of the day similar to those on the experimental day. Heart rate, mean arterial blood pressure, and self-assessed sense of energy were recorded at the time of each test. RESULTS: Reaction time for digit-symbol substitution test increased, delayed memory was degraded, mean arterial pressure and energy level decreased, and heart rate increased at a hemoglobin concentration of 5.7 g/dl (all P < 0.05). Increasing Pao2 to 406 +/- 47 mmHg reversed the digit-symbol substitution test result and the delayed memory changes to values not different from those at the baseline hemoglobin concentration of 12.7 +/- 1.0 g/dl, and decreased heart rate (P < 0.05). However, mean arterial pressure and energy level changes were not altered with increased Pao2 during acute anemia. CONCLUSION: The authors confirmed that acute isovolemic anemia subtly slows human reaction time, degrades memory, increases heart rate, and decreases energy level. The findings of this study support the hypothesis that increasing Pao2 to 350 mmHg or greater by breathing oxygen reverses all of these effects of acute anemia except for decreased energy.

Heart rate increases linearly in response to acute isovolemic anemia.

BACKGROUND: The cardiovascular response to acute isovolemic anemia in humans is thought to differ from that of other species. Studies of anesthetized humans have found either no change or a decreased heart rate. A previous study showed that in 32 healthy unmedicated humans, heart rate increased during acute isovolemic anemia. The hypothesis that heart rate in humans increases in response to acute isovolemic anemia and that the increase is affected by gender was tested. STUDY DESIGN AND METHODS: Acute isovolemic anemia to a Hb concentration of approximately 5 g per dL in 95 unmedicated healthy humans was produced by simultaneous withdrawal of blood and IV replacement with 5-percent HSA and autologous platelet-rich plasma. The relationship between heart rate and Hb concentration was examined using a mixed-effects linear regression model that allowed each person to have a fitted line with its own slope and intercept. Cubic and quadratic terms were added to determine if these improved the goodness of fit. The effect of gender was tested by including it and its interactions with Hb in the mixed model. RESULTS: The relationship between heart rate and Hb concentration was linear (p < 0.001) and consistent among the population studied: heart rate = 116.0-4.0 [Hb] (slope 95% CI: -4.2 to -3.8 beats/min/g Hb). Adding a cubic or quadratic term did not significantly improve the goodness of fit of the mathematical expression to the data, confirming the linear nature of the relationship between heart rate and Hb concentration. For women, the slope of the heart rate response was significantly greater than it was for males (difference +/- SE: 0.70 +/- 0.23, p < 0.005). CONCLUSION: In 95 unmedicated, healthy humans, heart rate was a linear function of Hb during acute isovolemic anemia. Females had a significantly greater slope of increase in heart rate with decreasing Hb concentration than did males. The relationship is consistent among individuals, is similar to that reported for conscious dogs, and differs from that found previously in anesthetized humans.

Acute isovolemic anemia does not impair peripheral or central nerve conduction.

BACKGROUND: Previous studies have found subtle slowing of responses in tests of addition and digit-symbol substitution during acute severe isovolemic anemia to a hemoglobin concentration of 5 g/dl in healthy unmedicated humans. In this study, the authors tested the hypothesis that such changes relate to the slowing of afferent neural traffic. METHODS: The median nerve was stimulated at the wrist in seven healthy unmedicated volunteers before and after induction of acute isovolemic anemia to a nadir hemoglobin concentration of 5.1 +/- 0.3 g/dl (mean +/- SD). Times for neural impulses to travel from the stimulus site to the brachial plexus, cervical spinal cord, and cerebral cortex were measured using somatosensory evoked potentials. Tests were repeated during acute anemia with the subject breathing oxygen. As a control for time and intrasubject variation, the testing was repeated on a separate day when anemia was not produced at times equivalent to those on the experimental day. RESULTS: Induced acute severe isovolemic anemia decreased nerve conduction latencies from the wrist to the contralateral cerebral cortex (i.e., to the N20 peak) by 2.3 +/- 1.6% compared with values at a mean hemoglobin concentration of 12.7 g/dl (P < 0.01). These decreased latencies were due solely to an increased peripheral conduction velocity, from the wrist to the brachial plexus (P < 0.05), and were not altered when subjects breathed oxygen (P > 0.05). Conduction velocity from the brachial plexus or cervical spinal cord to the cerebral cortex did not change with acute anemia (P > 0.05). Latencies did not differ on the control day among the times of testing (all P > 0.05), nor did they differ at baseline between the control and experimental days (all P > 0.05). CONCLUSION: Somatosensory evoked potential latencies were not increased by acute severe isovolemic anemia, making it unlikely that the afferent portion of the neural system is responsible for slowing of cognitive responses previously observed during acute anemia. Because severe isovolemic anemia did not increase somatosensory evoked potential latencies, etiologies other than anemia should be sought if latencies are increased during intraoperative monitoring.